The Baltimore Longitudinal Study of Aging (BLSA) prostate aging and disease study has both retrospective and prospective arms involving repeated assessments of anatomical, physiological, hormonal, and behavioral aspects of age-associated changes in prostate size. A major goal of the study is to identify antecedents of prostate cancer and benign prostatic hyperplasia (BPH). Prostate specific antigen (PSA) has become a useful screening tool for prostate cancer identifying men with cancer more than 5 years earlier than without screening. Early risk assessment with PSA can potentially identify men who would benefit from more frequent surveillance, and in the selection of high risk cohorts for prostate cancer prevention trials and preventive measures as they become available. Over the past eighteen months, we have reported 3 studies that address the use of PSA. The first study demonstrated that PSA is an early marker identifying men at high risk of prostate cancer. In men 40 to 60 years of age, the risk for cancer was increased almost 4 fold over a 25 year period when PSA was above the median (.6 to .7) as compared to being below it. The second study 2 examined a potential strategy for improving diagnosis of prostate cancer in men who have PSA values in the 2 to 4 ng/ml range, where risk is known to be increased in men less than 60 years. The relative risk of prostate cancer was found to be 6.5 greater when the PSA velocity was 0.1 ng/mL/year or more compared with a velocity of less than 0.1 ng/mL/year for 40 to 60 year old men with PSA in the 2 to 4 ng/ml range. The third study explored whether "elevated" PSA levels identify men at increased risk for developing prostate enlargement over a 20-30 year period. The relative risk of prostate enlargement was 3- to 6-fold higher for men 40 to 49.9 years old with a PSA of 0.31 ng./ml. or more compared to men with PSA levels of 0.30 ng./ml. or less at baseline. The relative risk was increased 5- to 9-fold in men 50 to 59.9 years old and 11-fold in those 60 to 69.9 years old when comparing men with PSA greater than 0.80 ng./ml. and greater than 1.70 ng./ml. with those with PSA 0.50 or less. The probability of freedom from prostate enlargement at 20 years was 0.89 and 0.63 for men 40 to 49.9 years old with PSA levels below and above 0.30 ng./ml. For men 50 to 59.9 years old the 10-year probability of freedom from prostate enlargement was 0.90 and 0.59 when PSA levels were below and above 0.80 ng./ml. At age 60 to 69.9 years the 10-year probability of freedom from prostate enlargement was 0.83 and 0.27 when PSA levels were below and above 1.70 ng./ml. The three studies suggest that PSA allows for the early identification of men at increased risk for the future development of prostate cancer and benign prostatic hyperplasia over up to 30 years. The ability to stratify men offers a means to identify those requiring closer surveillance, and may represent men who would benefit from preventive measures as they are identified. The ability to identify men at increased risk, suggests the need to identify preventive strategies to minimize risk. We have examined some factors that may be associated with increased prostate cancer risk. Over the past several years, we have examined several such factors including the risk of prostate cancer associated with having an enlarged prostate gland, the impact of a low serum selenium, and insulin like growth factors (IGF) on prostate cancer. Over the past year, we have explored the role of dietary factors in BLSA men. We have examined the association of total energy intake and macronutrient contributors to energy with prostate cancer risk using a food frequency questionnaire. Total energy intake was positively associated with prostate cancer with a 3.8 fold increased risk when comparing the highest to lowest quintile of energy intake. Energy-adjusted intake of protein, fat, and carbohydrate were not statistically significantly associated with prostate cancer risk. In addition, no association was found between plasma vitamin C concentrations within the normal range and the risk of prostate cancer.